Vasoactive Intestinal Polypeptide Inhibits Pacemaker Activity via the Nitric Oxide-cGMP-Protein Kinase G Pathway in the Interstitial Cells of Cajal of the Murine Small Intestine

  • Kim, Byung Joo (Department of Physiology and Biophysics, Seoul National University College of Medicine) ;
  • Lee, Jae Hwa (Department of Physiology and Biophysics, Seoul National University College of Medicine) ;
  • Jun, Jae Yeoul (Department of Physiology, Chosun University College of Medicine) ;
  • Chang, In Youb (Department of Physiology, Chosun University College of Medicine) ;
  • So, Insuk (Department of Physiology and Biophysics, Seoul National University College of Medicine) ;
  • Kim, Ki Whan (Department of Physiology and Biophysics, Seoul National University College of Medicine)
  • Received : 2005.09.07
  • Accepted : 2006.05.01
  • Published : 2006.06.30

Abstract

Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous depolarization (pacemaker potentials) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of vasoactive intestinal polypeptide (VIP) on the pacemaker potentials in cultured ICCs from murine small intestine were investigated by whole-cell patch-clamp techniques. Addition of VIP (50 nM-$1{\mu}M$) decreased the amplitude of pacemaker potentials and depolarized resting membrane potentials. To examine the type of receptors involved in ICC, we examined the effects of the $VIP_1$ agonist and found that it had no effect on pacemaker potentials. Pretreatment with $VIP_1$ antagonist ($1{\mu}M$) for 10 min also did not block the VIP (50 nM)-induced effects. On the other hand exposure to 1H-(1,2,4)oxadiazolo(4,3-A)quinoxalin-1-one (ODQ, $100{\mu}M$), an inhibitor of guanylate cyclase, prevented VIP inhibition of pacemaker potentials. Similarly KT-5823 ($1{\mu}M$) or RP-8-CPT-cGMPS ($10{\mu}M$), inhibitors of protein kinase G (PKG) blocked the effect of VIP (50 nM) on pacemaker potentials as did N-nitro-L-arginine (L-NA, $100{\mu}M$), a non-selective nitric oxide synthase (NOS) inhibitor. These results imply that the inhibition of pacemaker activity by VIP depends on the NO-cGMP-PKG pathway.

Keywords

cGMP;Interstitial Cells of Cajal;Nitric Oxide;Protein Kinase G;Vasoactive Intestinal Polypeptide

Acknowledgement

Supported by : Korea Science and Engineering Foundation

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